Clinical significance of low expression of Prostasin mRNA in human gastric cancer.
BACKGROUND
Prostasin is considered to have suppressive activities against tumor progression. The aim of this study was to clarify its clinical significance in gastric cancer.


METHODS
Tumor and the corresponding normal samples were prepared from a total of 108 gastric cancer patients. Prostasin expression was assayed by real time reverse transcription (RT)-polymerase chain reaction (PCR) and by immunohistochemistry. Epigenetic silencing of the expression was examined by demethylation treatment. Survival was examined in Kaplan-Meier plots, and the relationship between its expression and clinicopathologic factors was statistically analyzed.


RESULTS
Prostasin mRNA expression was significantly down-regulated in tumor tissues. Immunohistochemistry confirmed loss of Prostasin expression in gastric cancer. Gastric cancer cell lines that did not express Prostasin mRNA retrieved its expression following demethylation treatment. In those patients whose tumor expressed Prostasin mRNA at reduced levels, we observed shorter survival (P = 0.0110), due to a higher incidence of lymph node metastasis (P = 0.0087), lymphatic permeation (P = 0.0542) and venous permeation (P = 0.0492).


CONCLUSIONS
Prostasin mRNA expression was frequently down-regulated in gastric cancer. Loss of expression might be regulated by epigenetic factors, contributing to the shorter survival. Reduced Prostasin mRNA expression might be a novel indicator for biological aggressiveness in gastric cancer.
Sakashita
Katsuya
K
Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan.
Mimori
Koshi
K
Tanaka
Fumiaki
F
Tahara
Kouichirou
K
Inoue
Hiroshi
H
Sawada
Tetsuji
T
Ohira
Masaichi
M
Hirakawa
Kosei
K
Mori
Masaki
M
D000368:Aged; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality*; D000099271:Prostasin
D012333:RNA, Messenger; D012697:Serine Endopeptidases; D000099271:Prostasin